Research in this section consists of studies on the physical and chemical properties of proteins of biological interest and the roles of ligand binding and protein-protein interactions in enzyme catalysis and regulation. (1) Active-site ligand interactions with dodecameric glutamine synthetase from E. coli have been studied by spectrophotometric, binding and calorimetric techniques using the diastereoisomers of L-met-S,R-sulfoximine separately and together. Conformational differences between unadenylylated and adenyllylated enzyme forms on binding active-site ligands have been detected. (2) Reactivation of glutamine synthetase after auto-inactivation with L-met-S-sulfoximine, ATP, and Mn++ (or Mg++) has been accomplished. The reactivation of the enzyme is first order dependent on the 3rd-4th power of (H+), and coincides with the release/submit of 2 Mn++, L-met-S-sulfoximine-P, and ADP; increasing the pH from less than or equal to 5 to greater than 6 produces reinactivation. Inter- and intra-subunit bonding domains are markedly stabilized in the inactive enzyme complex. (3) Equilibrium and kinetic studies of Mn++-glutamine synthetase interactions (using metal ion-dye chelators and pH indicator dyes) have provided information on the structural and catalytic roles of Mn++.